title: Identification of α-taxilin as an essential factor for the life cycle of hepatitis B virus.
abstract: OBJECTIVE
  α-taxilin was identified as binding partner of syntaxins and is supposed to regulate vesicular trafficking. However, the physiological functions of α-taxilin and its potential relevance for the life cycle of hepatitis B virus (HBV) are still poorly understood.
  
  
  METHODS
  Transfected hepatoma cells, infected primary human hepatocytes, and liver tissue of HBV-infected patients were used to study the expression of α-taxilin. Subcellular localization and colocalization were analyzed by confocal laser scanning microscopy (CLSM). Protein-protein interactions were further investigated by co-immunoprecipitations. Silencing of α-taxilin expression was performed by lentiviral gene transfer.
  
  
  RESULTS
  HBV producing cells show a significant higher level of α-taxilin. HBV induces α-taxilin expression, by its regulatory proteins HBx and LHBs via c-Raf. This indicates that α-taxilin is essential for the release of HBV particles. CLSM and co-immunoprecipitations demonstrated that the PreS1PreS2 domain of LHBs interacts with α-taxilin. α-taxilin harbors a YXXL motif that represents a classic late domain. In accordance with this, it was found by co-immunoprecipitations that α-taxilin interacts with the ESCRT I component tsg101. CLSM revealed that a fraction of α-taxilin colocalizes with LHBs and tsg101.
  
  
  CONCLUSIONS
  α-taxilin plays an essential role for release of HBV-DNA containing particles. It might act as an adapter that binds, on the one hand, to LHBs and, on the other hand, to tsg101 and thereby helps recruit the ESCRT machinery to the viral envelope proteins.
authors.affiliation: Paul-Ehrlich-Institute, Division of Virology, D-63325 Langen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Caroline
authors.initials: C
authors.lastname: Boehm
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Himmelsbach
authors.forename: Christian
authors.initials: C
authors.lastname: Donnerhak
authors.forename: Hendrik
authors.initials: H
authors.lastname: Roettger
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Weiss
authors.forename: Daniela
authors.initials: D
authors.lastname: Ploen
authors.forename: Eberhard
authors.initials: E
authors.lastname: Hildt
mesh_terms: D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D006515:Hepatitis B virus / Q000254:growth & development* / Q000502:physiology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D008018:Life Cycle Stages / Q000502:physiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000032:analysis / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D019908:Proto-Oncogene Proteins c-raf; D014157:Transcription Factors; D033921:Vesicular Transport Proteins; D054334:Viral Regulatory and Accessory Proteins; D000099177:Tsg101 Protein; C488100:TXLNA protein, human
keywords: CLSM; EIAV; ESCRT; HBV; HBx; HCC; LHBs; MVB; Morphogenesis; RCC; SHBs; SVP; Signal transduction; TXLN; confocal laser scanning microscopy; endosomal sorting complex required for transport; equine infective anemia virus; hepatitis B virus; hepatocellular carcinoma; large hepatitis B virus surface antigen; multivesicular body; renal cell carcinoma; small ….; subviral particle; tdn; transdominant negative; α-taxilin gene